Noncovalent interactions
Noncovalent interactions:
Lecture 2: Chemical Foundations II
Ionic interactions Hydrogen bonds Van der Waals interactions Hydrophobic effext
Noncovalent interactions: Ionic interactions + - + - + + - +
+ H20
Noncovalent interactions: Ionic interactions
+ -
close contact protein-protein: water excluded = strong interaction
NaCl strong interaction
weak interaction -
+
“hydration shell” must be removed for direct interaction with protein
1
Hydration shell and selectivity of ion K+ channels
Hydration shell and selectivity of ion K+ channels
-> selectivity = 1000x!
Noncovalent interactions: Hydrogen bonds
Solubility in water depends on ability to establish hydrogen bonds
liquid water = dynamic network of hydrogen bonds
2
Noncovalent interactions: Van der Waals intereactions
Noncovalent interactions: Hydrophobic effect
Ex: O=O
result from transient dipoles occur in all types of molecules form only when atoms very close weak -> significant only if multiple and/or conjunction with other non-covalent bonds
Nonpolar molecules: Hydrophobic effect + Van der Waals forces
Specificity of association between biological macromolecules is based on multiple noncovalent interactions precisely spatially organized
nonpolar molecules stick together away from water
3
Building macromolecules “monomers”
Building macromolecules
“polymers”
Building macromolecules
Building macromolecules
dehydration
Peptide (amide) bond
!
4
Building macromolecules
Building macromolecules
phosphodiester bond
glycosidic bond
Large structures based on noncovalent bonds: cytoskeleton
Large structures based on non-covalent bonds: lipid membranes H-bonds, ionic interactions
water
actin filament
‘leaflets’
microtubule
Non-covalent bonds = easy to form and undo -> Polymers very dynamic
water
Van der Waals + hydrophobic interactions
hydrophobic environment
Weak interactions, lipids can move very rapidly within one leaflet = ‘2D liquid’
5
Which of the following molecules are membrane permeable?
Construction of reagents that become trapped and accumulate in the cytoplasm Fluorescent molecule modified by coupling via a carboxyl group to an acetyl group. Note that the resulting molecule is non-polar. cell
• Benzene • Calcium • Sugars
Esterase C
Plasma membrane
(enzyme that hydrolyzes ester bonds)
O
O H C H
Charged/hydrophilic molecules cannot cross membranes unless recognized by special protein channels/transporters
H C H H
Question: Explain why the cells incubated in a medium containing a low concentration of this reagent will appear very brightly fluorescent.
Hydrophobic amino acids
Building blocks: Amino acids
link to next aa (COO- )
α-carbon
H
+H
C
amine
3N
R
base + acid = amphoteric COO-
link to next aa (NH3+ )
acid Side chain = “R group”
R: 20 different shapes + charges + other properties -> each amino acid has its own “personality”
6
Hydrophobic amino acids
Hydrophilic amino acids
Most of the hydrophobic aa have similar chemical properties. However, each side chain has a different shape and occupies a different volume.
P
Hydrophilic amino acids
Hydrophilic amino acids
moderately basic strongly basic
weakly basic
7
Hydrophilic amino acids
Aspartic acid
Glutamic acid
Hydrophilic amino acids
-> hydrogen bonds
similar acid strengths, different lengths
Hydrophilic amino acids
“Special” amino acids
:O : H
-> hydrogen bonds
8
“Special” amino acids
“Special” amino acids
small, fits in tight spaces
rigid bond fixed angle -> kink to the polypeptide chains
Cysteine
disulfide bridge
Cysteine reduced
cytoplasm reducing ambient
oxidized
extracellular space (e.g. plasma!) oxidizing ambient
disulfide bridge
9
Building blocks: Sugars
Building blocks: Sugars
carbohydrates -> C + H2O = CH2O chemical groups: many OH + aldehyde or ketone large variety of geometries -> high specificity of interactions
Building blocks: Sugars
Building blocks: Sugars
branching
modification
10
Lecture 2: Chemical Foundations II
Ionic interactions Hydrogen bonds Van der Waals interactions Hydrophobic effext
Noncovalent interactions: Ionic interactions + - + - + + - +
+ H20
Noncovalent interactions: Ionic interactions
+ -
close contact protein-protein: water excluded = strong interaction
NaCl strong interaction
weak interaction -
+
“hydration shell” must be removed for direct interaction with protein
1
Hydration shell and selectivity of ion K+ channels
Hydration shell and selectivity of ion K+ channels
-> selectivity = 1000x!
Noncovalent interactions: Hydrogen bonds
Solubility in water depends on ability to establish hydrogen bonds
liquid water = dynamic network of hydrogen bonds
2
Noncovalent interactions: Van der Waals intereactions
Noncovalent interactions: Hydrophobic effect
Ex: O=O
result from transient dipoles occur in all types of molecules form only when atoms very close weak -> significant only if multiple and/or conjunction with other non-covalent bonds
Nonpolar molecules: Hydrophobic effect + Van der Waals forces
Specificity of association between biological macromolecules is based on multiple noncovalent interactions precisely spatially organized
nonpolar molecules stick together away from water
3
Building macromolecules “monomers”
Building macromolecules
“polymers”
Building macromolecules
Building macromolecules
dehydration
Peptide (amide) bond
!
4
Building macromolecules
Building macromolecules
phosphodiester bond
glycosidic bond
Large structures based on noncovalent bonds: cytoskeleton
Large structures based on non-covalent bonds: lipid membranes H-bonds, ionic interactions
water
actin filament
‘leaflets’
microtubule
Non-covalent bonds = easy to form and undo -> Polymers very dynamic
water
Van der Waals + hydrophobic interactions
hydrophobic environment
Weak interactions, lipids can move very rapidly within one leaflet = ‘2D liquid’
5
Which of the following molecules are membrane permeable?
Construction of reagents that become trapped and accumulate in the cytoplasm Fluorescent molecule modified by coupling via a carboxyl group to an acetyl group. Note that the resulting molecule is non-polar. cell
• Benzene • Calcium • Sugars
Esterase C
Plasma membrane
(enzyme that hydrolyzes ester bonds)
O
O H C H
Charged/hydrophilic molecules cannot cross membranes unless recognized by special protein channels/transporters
H C H H
Question: Explain why the cells incubated in a medium containing a low concentration of this reagent will appear very brightly fluorescent.
Hydrophobic amino acids
Building blocks: Amino acids
link to next aa (COO- )
α-carbon
H
+H
C
amine
3N
R
base + acid = amphoteric COO-
link to next aa (NH3+ )
acid Side chain = “R group”
R: 20 different shapes + charges + other properties -> each amino acid has its own “personality”
6
Hydrophobic amino acids
Hydrophilic amino acids
Most of the hydrophobic aa have similar chemical properties. However, each side chain has a different shape and occupies a different volume.
P
Hydrophilic amino acids
Hydrophilic amino acids
moderately basic strongly basic
weakly basic
7
Hydrophilic amino acids
Aspartic acid
Glutamic acid
Hydrophilic amino acids
-> hydrogen bonds
similar acid strengths, different lengths
Hydrophilic amino acids
“Special” amino acids
:O : H
-> hydrogen bonds
8
“Special” amino acids
“Special” amino acids
small, fits in tight spaces
rigid bond fixed angle -> kink to the polypeptide chains
Cysteine
disulfide bridge
Cysteine reduced
cytoplasm reducing ambient
oxidized
extracellular space (e.g. plasma!) oxidizing ambient
disulfide bridge
9
Building blocks: Sugars
Building blocks: Sugars
carbohydrates -> C + H2O = CH2O chemical groups: many OH + aldehyde or ketone large variety of geometries -> high specificity of interactions
Building blocks: Sugars
Building blocks: Sugars
branching
modification
10
